Project Summary/Abstract A vital feature of sensory systems is the ability to adjust sensitivity based on environmental demands. This process takes place through neuromodulation. The mechanisms underlying neuromodulation are poorly understood, despite the fact that it is a necessary mechanism for survival. This project aims to determine how the neuromodulator octopamine (OA), the insect correlate of noradrenaline, tunes motion-detecting circuits in the Drosophila optic lobe to become more sensitive to faster motion. These circuits are well characterized and provide a powerful model system to study the effects of behavior on circuit output. They consist of connections between photoreceptors and lobula plate tangential cells (LPTCs). Locomotion modulates LPTCs by increasing their response amplitude and shifting their sensitivity toward faster moving stimuli. Thus, moving flies speed up their reaction time by modulating LTPCs to respond optimally to the increased relative speed of the visual scene around them. This process is regulated by the release of octopamine (OA), a neuromodulator equivalent to mammalian norepinephrine. However, the mechanism of OA modulation in this circuit is unknown. Experiments in the comparable visual systems of blowflies and hoverflies show that the effect of OA is exerted upstream of LPTCs. Additionally, as OA receptors are not evenly distributed amongst different cell types in the optic lobe, it is unlikely that OA tunes the circuit by causing a global shift in cellular processing properties. Here, I focus on cells in the medulla of the Drosophila optic lobe. Compared to other cell types in the motion vision pathway, medulla cells express high levels of OA receptors and show changes in their temporal processing properties when exposed to an OA agonist. Thus, I hypothesize that OA modulates the tuning of Drosophila motion detectors by causing medulla cells to selectively propagate faster visual information. I will explore this hypothesis through two aims: (1) characterizing the temporal processing properties of specific cells in the circuit before and after OA application, and (2) investigating the mechanisms underlying the changes in processing properties.